This invention relates to methods of generating novel progeny from fungi to produce new biological activities not detectable in the parents.
Secondary metabolites produced by microorganisms, such as fungi, reflect a wide variety of chemical structures affecting numerous biological activities in different classes of organisms, including both prokaryotes (bacteria) and eukaryotes (animals, plants, and insects). Antibiotics constitute the largest group of known bioactive secondary metabolites, acting on such diverse processes as cell wall synthesis, DNA replication, and protein synthesis. In addition to their use as antibiotics, secondary metabolites are being successfully developed and used in agriculture as pesticides, herbicides, and anti-parasitic compounds, and in treating non-infectious human diseases as inhibitors of enzyme activity, as immunomodulators, and as anti-hypersensitivities. There are a number of reasons for the urgency in the expansion and intensification of the search for new useful secondary metabolites. Among these reasons are the need for less toxic, more potent antibiotics, the evolving resistance to existing antibiotics, emergence of new viral diseases, and related factors of concern in agriculture.
It is estimated that there are a minimum of 1.5 million species of fungi. About 70,000 species of fungi have been described in the literature (Hawksworth, Mycol. Res. 95:441-452, 1991), and only about 5,000 of these have been documented as producers of secondary metabolites (Porter et al., Pestic. Sci. 39:161-168, 1993). These observations have exciting implications for the discovery of large numbers of new bioactive secondary metabolites from known fungi, and further indicate that the world's undiscovered fungi can be viewed as a massive potential resource of new secondary metabolites.